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1.
J Thorac Dis ; 16(4): 2637-2643, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38738217

ABSTRACT

Background and Objective: Extracorporeal membrane oxygenation (ECMO) has historically been utilized as a temporary life support option for patients with severe cardiac and pulmonary dysfunction. Recent advancements have enabled the safe application of ECMO in a wider variety of patients; we present a review of its use in patients undergoing general thoracic procedures supported by a case series at our institution. Methods: We review current literature focusing on ECMO applications in thoracic surgery outside of the traditional use. Additionally, we offer three cases of ECMO utilization to illustrate success stories and key lessons learned regarding the use of ECMO in general thoracic surgery. Key Content and Findings: Technologic advancements and enhanced safety profiles have enabled the safe application of ECMO in a wide array of patients far beyond the historic indications of cardiogenic shock and acute respiratory distress syndrome (ARDS). It is now feasible to consider ECMO for management of acute thoracic emergencies, as well as to better facilitate operative safety in complex general thoracic surgical procedures. Both venovenous and venoarterial ECMO can be utilized in carefully selected patients to provide cardiopulmonary support while enabling improved visualization and increased mobilization without concern for respiratory and/or cardiac compromise. Conclusions: Enthusiasm for the use of ECMO has increased in recent years. What was once considered a salvage therapy in cases of life-threatening cardiopulmonary decompensation now plays an increasingly important role in the safe conduct of complex thoracic surgery procedures, provides much needed time for organ recovery, and offers acute resuscitation options. This shift broadens our ability to deliver life-saving care to patients that previously would have otherwise had limited treatment options.

2.
Transplantation ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771067

ABSTRACT

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

3.
Article in English | MEDLINE | ID: mdl-38508486

ABSTRACT

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

5.
Front Immunol ; 15: 1341675, 2024.
Article in English | MEDLINE | ID: mdl-38380332

ABSTRACT

Primary Graft Dysfunction (PGD) is a major cause of both short-term and long-term morbidity and mortality following lung transplantation. Various donor, recipient, and technical risk factors have been previously identified as being associated with the development of PGD. Here, we present a comprehensive review of the current literature as it pertains to PGD following lung transplantation, as well as discussing current strategies to mitigate PGD and future directions. We will pay special attention to recent advances in lung transplantation such as ex-vivo lung perfusion, thoracoabdominal normothermic regional perfusion, and up-to-date literature published in the interim since the 2016 ISHLT consensus statement on PGD and the COVID-19 pandemic.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Humans , Primary Graft Dysfunction/etiology , Pandemics , Lung Transplantation/adverse effects , Lung , Risk Factors
7.
Ann Thorac Surg ; 117(4): 820-827, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37625610

ABSTRACT

BACKGROUND: After implementation of the Lung Allocation Score in 2005, idiopathic pulmonary fibrosis (IPF) emerged as the most common indication for lung transplantation (LT) in the United States. The age and comorbidity of patients undergoing LT have since increased, and the indications for LT have evolved. However, limited data have been used to analyze more recent outcomes among the IPF population. METHODS: This study analyzed LTs for the primary indication of IPF by using the United Network for Organ Sharing database. An eras-based analysis was performed, comparing patient characteristics, survival, and related outcomes during 2005 to 2009 (era 1) and 2010 to 2014 (era 2) with χ2, Wilcoxon rank sum, and Kaplan-Meier analyses. The study compared 1-year survival from 2005 to 2020 and survival at milestones ranging from 1 month to 5 years. Two adjusted Cox proportional hazards models were conducted: 5-year survival by era and 1-year survival annually from 2010 to 2020. RESULTS: From era 1 (n = 1818) to era 2 (n = 3227), the median age of LT recipients increased from 61 to 63 years (P < .001). The percentage of patients in the intensive care unit before LT climbed from 7.7% to 12.1% (P < .001), and the percentage of patients with diabetes grew from 17.9% to 19.4% (P = .003). Despite increased severity of illness, 5-year survival increased from 51.9% in era 1 to 55.2% in era 2 (P = .02). Adjusted modeling indicated that LT during era 2 featured a 17% hazard reduction compared with era 1 (hazard ratio, 0.83; 95% CI, 0.76-0.91). CONCLUSIONS: Survival is improving for patients undergoing LT for IPF, despite the challenges of transplant recipients with progressively higher risk profiles.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Transplantation , Tissue and Organ Procurement , Humans , United States/epidemiology , Middle Aged , Registries , Retrospective Studies , Idiopathic Pulmonary Fibrosis/surgery , Proportional Hazards Models
8.
Transplantation ; 108(4): 1015-1020, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38049940

ABSTRACT

BACKGROUND: With increasing life expectancy, patients with HIV are more commonly acquiring other chronic diseases, such as end-stage lung disease, for which transplant may be the only effective solution. Until recently, HIV infection was considered a contraindication to lung transplant (LTx). As LTx in people living with HIV (PLWH) becomes more common, there remain limited data on outcomes in this population. METHODS: Using the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, we identified LTx recipients with HIV by either serostatus or nucleic acid testing. A control group of confirmed HIV-negative LTx recipients was propensity score matched on age, body mass index, primary diagnosis, and year of transplant. Patient characteristics, transplant parameters, survival, and postoperative outcomes were compared. RESULTS: Fifty-nine LTx recipients with HIV were identified and compared with 236 HIV-negative controls. Among PLWH, cytomegalovirus status was more frequently positive (76.3% versus 58.9%, P = 0.014), and the median Lung Allocation Score at match was higher (44 versus 39, P = 0.004). PLWH were more likely to undergo dialysis postoperatively (18.6% versus 8.9%, P = 0.033), although other complication rates were similar. Fifty-three percent of LTx for PLWH occurred since 2020. One-year survival for PLWH was 91.2% versus 88.6% for controls ( P = 0.620). Three-year survival for a smaller subset was also not statistically significant (HIV versus control: 82.6% versus 77.8%, respectively, P = 0.687). CONCLUSIONS: There was no difference in 1-y survival for LTx recipients living with HIV compared with a matched control group, supporting this group of patients as viable candidates for LTx.


Subject(s)
HIV Infections , Lung Transplantation , Tissue and Organ Procurement , Humans , HIV Infections/complications , HIV Infections/diagnosis , Retrospective Studies , Lung Transplantation/adverse effects , Propensity Score
9.
Surg Open Sci ; 16: 248-253, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076572

ABSTRACT

Objective: Traditionally, critically ill patients requiring prolonged mechanical ventilation benefit from a long-term airway, thus necessitating tracheostomy. The widespread application of extracorporeal membrane oxygenation (ECMO) has exponentially increased in recent years, creating a new subset of patients necessitating tracheostomy with significantly increased bleeding risk. We present a hybrid dilational tracheostomy technique utilizing a Rummel tourniquet developed at our institution to mitigate bleeding risk in patients on ECMO necessitating long-term airway. Methods: A total of 24 patients on ECMO underwent bedside hybrid dilational tracheostomy with utilization of a Rummel tourniquet from 06/2020 to 01/2022 at our institution. These patients were followed longitudinally and evaluated for postoperative bleeding. Particular attention was paid to anticoagulation regimens pre- and post-operatively. Results: The primary outcome of the study, postoperative bleeding, was observed in four of the 24 study participants (16.67 %). Each of these complications were managed with tightening of the Rummel tourniquet and application of hemostatic packing agents; no operative interventions were required. Anticoagulation was held for a mean time of 4.33 h preoperatively and 5.2 h postoperatively. Conclusions: Our data support this hybrid tracheostomy technique with the addition of a Rummel tourniquet to be a safe and effective adjunct for perioperative hemostasis in high-risk patients necessitating tracheostomy while on ECMO. While this technique was initially developed for critically ill COVID-19 patients, we believe it can be applied to all patients on ECMO to help mitigate perioperative bleeding risk.

10.
J Thorac Dis ; 15(9): 5064-5073, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37868886

ABSTRACT

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

11.
JTCVS Tech ; 20: 176-181, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37555057

ABSTRACT

Objective: Lobar torsion is a rare occurrence in which a portion of the lung is twisted on its bronchovascular pedicle. The vast majority are observed in the acute postoperative period often following right upper lobectomy. Spontaneous middle lobe torsion independent of pulmonary resection is exceptionally rarer; fewer than 15 cases have been recorded. We present an institutional case series of 2 patients postorthotopic liver transplantation who developed spontaneous middle lobe torsion due to large pleural effusions. Methods: We provide the medical course as well as intraoperative techniques for our 2 patients along with a review of the literature. Results: Both patients in this case series underwent orthotopic liver transplant complicated postoperatively by a large pulmonary effusion. Patient one developed an abdominal hematoma requiring evacuation and repair, after which he developed progressive shortness of breath. Bronchoscopy revealed a right middle lobe obstruction; upon thoracotomy, 180-degree torsion with widespread necrosis was evident and the middle lobe was removed. He is doing well to date. Patient 2 experienced postoperative pleural effusion and mucus plugging; computed tomography revealed abrupt middle lobe arterial occlusion prompting urgent operative intervention. Again, the middle lobe was grossly ischemic and dissection revealed a 360-degree torsion around the pedicle. It was resected. He is doing well to date. Conclusions: As the result of its rarity, radiographic and clinical diagnosis of spontaneous pulmonary lobar torsion is challenging; a high index of suspicion for spontaneous middle lobe torsion must be maintained to avoid delays in diagnosis. Prompt surgical intervention is essential to improve patient outcomes.

12.
Cancer Treat Res Commun ; 36: 100723, 2023.
Article in English | MEDLINE | ID: mdl-37327571

ABSTRACT

INTRODUCTION: Non-Small Cell Lung Cancer (NSCLC) diagnosed at a younger age have patterns of care, responses to treatment, and outcomes not entirely clear. A particular feature includes more advanced stages at diagnosis. Our objective was to characterize these young patients with advanced disease and evaluate the impact of targeted therapies. METHODS: Analyzing our cohort of 18,252 newly diagnosed NSCLC patients, we defined Young-age versus Norm-age based on the age distribution at the time of diagnosis. Stage-IV patients were investigated on their clinical information and outcomes; deaths were considered lung cancer-related. Primary outcome was overall survival (OS). Multivariate Cox models were built to evaluate independent prognostic factors in comparative age groups. RESULTS: We found 4,267 patients with stage-IV NSCLC (359 Young-age; 3,908 Norm-age). Young patients had predominance of females (52.6% vs. 43.3%, P = 0.001), never-smokers (43.2% vs. 14.8%, P < 0.001), and adenocarcinoma (73.5% vs. 62.5%, P < 0.001). Mean OS was 21.1 months in the Young and 15.1 months in Norm, respectively (P < 0.001). Young patients were more often treated with surgery (6.7% vs. 5.0%), chemotherapy (53.2% vs. 44.1%), and targeted therapy (10.6% vs. 5.7%). Molecular studies were assessed in patients when the mutation tests became clinically available (93 Young, 875 Norm) and revealed a critical role of targeted therapy in the improved survival of both age groups. DISCUSSION: Young patients with stage-IV NSCLC have a specific profile and benefit more when treated with surgery and targeted therapy. Molecular testing is critical in this population, where improved survival was identified. A more aggressive approach to this population needs to be considered.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Female , Humans , Male , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Biomarkers, Tumor/genetics , Proportional Hazards Models
13.
Cancer ; 129(6): 860-866, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36562086

ABSTRACT

BACKGROUND: There is a knowledge gap regarding lobar versus sublobar resection for atypical carcinoid (AC) of the lung. As such, the authors sought to understand and analyze the outcomes of sublobar resection versus lobectomy in this patient population. METHODS: A retrospective analysis using the National Cancer Database was performed to compare overall survival (OS) between patients treated with lobectomy and patients treated with sublobar resection for AC of the lung between the years 2004 and 2016. Patient characteristics were compared with χ2 tests. The Kaplan-Meier method was used to estimate OS distributions, and the log-rank test was used to compare distributions by treatment strategy. A multivariable Cox regression model was used to assess associations between the treatment strategy and OS. A propensity score matching method was also implemented to further eliminate treatment selection bias in the study sample. RESULTS: The database identified 669 patients with T1-T4 and N0-N3 lung ACs that were surgically resected. Unadjusted Kaplan-Meier survival curves did not demonstrate an OS difference between lobectomy and sublobar resection (p = .094). After propensity score matching, curves demonstrated a numerical improvement in OS with lobectomy; however, it was not statistically significant (p = .5). In a subgroup analysis, lobectomy and node-negative disease were associated with the best OS, whereas sublobar resection and node-positive disease were associated with the worst OS (p < .0001). Nodal involvement was associated with worse survival, regardless of surgical treatment (p < .0001). CONCLUSIONS: In patients with T1-T4 and N0-N3 ACs of the lung, lobectomy was not associated with an improvement in OS in comparison with sublobar resection.


Subject(s)
Carcinoid Tumor , Carcinoma, Neuroendocrine , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Retrospective Studies , Neoplasm Staging , Pneumonectomy/methods , Lung Neoplasms/pathology , Carcinoid Tumor/surgery , Lung/pathology
14.
J Extra Corpor Technol ; 54(1): 73-78, 2022 Mar.
Article in English | MEDLINE | ID: mdl-36380830

ABSTRACT

Extracorporeal life support, commonly referred to as extracorporeal membrane oxygenation (ECMO), is indicated when conventional medical and surgical measures fail to support a patient during cardiac or respiratory failure. Increased use of ECMO in recent years has led to innovation that has improved safety in appropriate candidates. This has resulted in the application of novel approaches to complex surgical problems. Herein, we describe a simple, novel, and new-to-market ECMO circuit used for successful perioperative veno-venous ECMO support of a patient undergoing complex repair of a tracheoesophageal fistula. We believe that this circuit and its use for intra-and post-operative extracorporeal support provides a framework for safe and simple ECMO support in the future, including perioperative support for patients undergoing complicated and challenging thoracic procedures.


Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Insufficiency , Tracheoesophageal Fistula , Humans , Extracorporeal Membrane Oxygenation/methods , Tracheoesophageal Fistula/surgery , Respiratory Insufficiency/therapy
15.
J Heart Lung Transplant ; 41(12): 1700-1711, 2022 12.
Article in English | MEDLINE | ID: mdl-36229329

ABSTRACT

BACKGROUND: In the US, only 23% of lungs offered for transplantation are transplanted. Ex vivo lung perfusion (EVLP) allows for evaluation of additional donor lungs; its adoption has been limited by resources and expertise. Dedicated facilities with a centralized lung evaluation system (CLES) could expand access to EVLP. METHODS: In this unblinded, nonrandomized, traditional feasibility study, 7 US transplant centers referred lungs declined for standard transplantation to a dedicated EVLP facility, which utilized a CLES. EVLP was remotely monitored by the transplant teams. CLES lungs were matched with contemporaneous conventional static cold-preserved controls at each center. RESULTS: A total of 115 recipients were enrolled, and 66 received allografts from 63 donors after EVLP at the dedicated CLES facility. Forty-nine contemporaneous patients served as controls. Primary graft dysfunction grade 3 at 72 hours (PGD3-72 hours) was higher in the CLES group with 16 (24%) vs 2 (4%) in the control (common RD 95% CI, 0.07-0.32; p = 0.0009). All recipients survived to 30 days and 1-year survival was similar for both groups (92% controls vs 89% CLES; common RD 95% CI, -0.14-0.08; p = 0.58). Total preservation time, hospital and ICU lengths of stay, and time to first extubation were longer in the CLES group. CONCLUSIONS: Remote ex vivo perfusion of lung allografts declined for conventional transplantation at a dedicated CLES facility is feasible and resulted in additional transplants. Recipients of allografts assessed with a CLES had a higher rate of PGD3-72 hours, but similar 30-day and 1-year outcomes compared to conventional lung recipients. (NCT02234128).


Subject(s)
Lung Transplantation , Humans , Extracorporeal Circulation , Lung , Lung Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Tissue Donors , Feasibility Studies
16.
Thorac Cardiovasc Surg Rep ; 11(1): e58-e60, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36187730

ABSTRACT

Background Lung cancer screening programs have increased the detection of early-stage lung cancer. High-resolution computed tomography can detect small, low-density pulmonary nodules, or ground-glass opacities. Obtaining a tissue diagnosis can be challenging, often necessitating surgical diagnosis. Preoperative localization and intraoperative fluoroscopy are valuable tools to guide resections for small pulmonary nodules. Case Description We present three cases using intraoperative fluoroscopy and Faxitron Bioptics that enhanced our certainty of resection of nonpalpable nodules. Conclusion We support the use of intraoperative fluoroscopy with the unique addition of Faxitron BioVision as safe and reliable methods to enhance the certainty of resection.

18.
Clin Nucl Med ; 47(12): e738-e739, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-35695721

ABSTRACT

ABSTRACT: A 39-year-old man presented with progressive dyspnea and lower extremity edema. Doppler ultrasound demonstrated bilateral leg partially occluded venous thromboses. A V/Q scan revealed a mismatched perfusion defect involving the entire right middle and lower lobes. Subsequent CT pulmonary angiogram revealed a mass lesion occluding the right interlobar pulmonary artery. Endobronchial ultrasound-guided fine-needle aspiration of the mass was concerning for neoplasm. 18 F-FDG PET/CT demonstrated marked hypermetabolism of the mass lesion. Patient underwent transmediastinal right pneumonectomy with histopathologic diagnosis of pulmonary artery angiomatoid fibrous histiocytoma, a rare etiology mimicking large pulmonary artery embolism.


Subject(s)
Histiocytoma, Benign Fibrous , Pulmonary Embolism , Male , Humans , Adult , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/pathology , Positron Emission Tomography Computed Tomography , Pulmonary Embolism/diagnostic imaging
20.
Transplantation ; 106(4): 879-886, 2022 04 01.
Article in English | MEDLINE | ID: mdl-33966025

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication in bilateral orthotopic lung transplant (BOLTx) recipients, but the contribution of intraoperative variables is not well defined. The authors hypothesized that intraoperative hypotension as well as hypoxia and vasopressor use would be associated with the development of postoperative AKI after BOLTx in patients without pre-existing renal dysfunction. METHODS: The authors performed a retrospective analysis of patients undergoing BOLTx at a single center between 2013 and 2017. Intraoperative variables of hemodynamics included duration of mean arterial pressure <55, <60, and <65 mm Hg; duration of oxygen saturation <90%; and vasoactive-inotropic score (VIS). Associations between the occurrence of AKI and intraoperative hypotension, hypoxemia, and VIS were evaluated while controlling for significant confounding variables. RESULTS: AKI occurred in 177 (72%) of 245 patients in postoperative days 1-7. Notable significant differences in univariate analyses included cumulative mechanical support time, maximum VIS, peripheral oxygen saturation <90% for >15 min, total minutes oxygen saturation <90%, and surgery duration in minutes. There was no significant difference in intraoperative hypotension measured as a duration >15 min for mean arterial pressure <55, <60, or <65 mm Hg. Multivariate logistic regression revealed preoperative creatinine (Odds ratio [OR], 7.77; confidence interval [CI], 1.96-30.83; P = 0.004), surgery duration (OR, 1.004; CI, 1.002-1.007; P = 0.002), and oxygen saturation (OR, 2.06; CI, 1.01-4.24; P = 0.049) <90% for >15 min to be independently associated with AKI. CONCLUSIONS: This study revealed that >15 min of intraoperative hypoxia was independently associated with postoperative AKI after BOLTx.


Subject(s)
Acute Kidney Injury , Lung Transplantation , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Lung Transplantation/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
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